The role of high loop gain induced by intermittent hypoxia in the pathophysiology of obstructive sleep apnoea

Intermittent hypoxia and unstable breathing are key features of obstructive sleep apnoea (USA), the most common pathological problem of breathing in sleep. Unstable ventilatory control is characterised by high loop gain (LG), and likely contributes to cyclical airway obstruction by promoting airway collapse during periods of low ventilatory drive. Potential new strategies to treat USA include manipulations designed to lower LG. However, the contribution of inherent versus induced LG abnormalities in USA remains unclear. Hence, a better understanding of the mechanisms causing high LG in USA is needed to guide the design of LG based treatments. USA patients exhibit abnormal chemoreflex control which contributes to increased LG. These abnormalities have been shown to normalise after continuous positive airway pressure treatment, suggesting induced rather than inherent trait abnormalities. Experimental intermittent hypoxia, mimicking USA, increases hypoxic chemosensitivity and induces long term facilitation; a sustained increase in ventilatory neural output which outlasts the original stimulus. These neuroplastic changes induce the same abnormalities in chemoreflex control as seen in USA patients. This review outlines the evidence to support that a key component of high LG in USA is induced by intermittent hypoxia, and is reversed by simply preventing this inducing stimulus. (C) 2014 Elsevier Ltd. All rights reserved.